CHAPTER 34. PRURITUS
Carol L. Scot
Because of the overall low prevalence of pruritus in the palliative care population, pruritus is not always included in the list of distressing symptoms to be addressed with palliation, but its relief matters greatly to the few people who have it. Severe pruritus can destroy sleep and diminish quality of life.
DEFINITION AND INCIDENCE
Pruritus, or itching, is the unpleasant sensation that provokes an urge to scratch. It generally involves a complex series of interactions among the skin, inflammatory processes, cutaneous nerves, and the central nervous system (Fleischer, 2000). Because minor or short-lived itching episodes rarely come to medical notice, the incidence of itching in the general population is not known. The lifetime experience of itching probably approaches 100%.
Researchers have attempted to assess the incidence and prevalence of itching in some subsets of patients. Pruritus occurs in about 30% of patients with psoriasis (Levine & Levine, 2004). Approximately 50% to 70% of patients with primary biliary cirrhosis experience pruritus (Talwalkar, Souto, Jorgensen et al., 2003). The fact that intractable pruritus can be an indication for liver transplantation demonstrates how severely pruritus can affect the quality of a person’s life (Terg, Coronel, Sorda et al., 2002). The prevalence of renal itch among patients on dialysis is estimated to be between 22% and 48% (Manenti, Vaglio, Costantino et al., 2005). In survivors of severe burns, the incidence of pruritus is as high as 87% (Field, Peck, Hernandez-Reif et al., 2000).
Even though much of the physiological basis of pruritus has been described, it is not completely understood, with the consequence that no specific antipruritic drug is available. “This is particularly unfortunate as, although itching is popularly perceived as a minor social or even humorous disability, it is frequently so severe and intractable as to cause the sufferer abject misery or even suicidal inclination” (Greaves & Wall, 1999, p. 487).
When itching is a major symptom in patients with far-advanced illness, all efforts need to be made to alleviate the discomfort, whether or not a precise cause is known.
ETIOLOGY AND PATHOPHYSIOLOGY
The sensation of itching appears to be the same in conditions as diverse as renal failure, insect bites, fungal infections, lymphoma, dry skin, liver failure, multiple sclerosis, and healing wounds, yet its pathophysiology in these conditions is not all the same, and treatments that work for some fail for others.
Itch can be cutaneous, neuropathic, neurogenic, mixed, or psychogenic.
In the skin, unmyelinated nerve fibers—C-fibers—mediate both cutaneous itch and pain. The C-fibers that mediate cutaneous itch cannot be differentiated anatomically from the ones that mediate pain, but they can be differentiated functionally (Fleischer, 2000; Twycross, Greaves, Handwerker et al., 2003). “The afferent C-fibres subserving this type of itch are a functionally distinct subset: they respond to histamine, acetylcholine and other pruritogens, but are insensitive to mechanical stimuli” (Twycross et al., 2003, p. 8).
Such C-fibers comprise about 5% of the C-fibers in human skin. Differentiation of the sensations of pain and itch may also depend on the specific anatomy and physiology of the person experiencing it. Acetylcholine causes itching in the skin of atopic patients, but when it is injected into the skin of nonatopic persons, it causes pain (Twycross et al., 2003).
Another similarity in the physiology of pain and itch is the phenomenon of severe pain or pruritus sensitizing an area around it. With pain, this is called allodynia, in which the skin interprets benign touch as pain. The area around an intensely pruritic area can similarly be sensitized to interpret light touch as intense itch (allokinesis) (Twycross et al., 2003).
Histamine plays a primary role in the pruritus of many commonly occurring itchy conditions such as insect bites, drug reactions, urticaria, and wound healing, but not in other conditions. Histamine receptors H 1 and H 2 are found in the skin.
Serotonin is less pruritogenic in the skin than histamine, but in some types of itch, such as cholestasis-related itching, it seems to play a major role (Fleischer, 2000). Serotonin can cause itch via both peripheral and central mechanisms. In the skin, it releases histamine from mast cells. The central mechanism is inferred because ondansetron (Zofran), a specific 5-HT 3 receptor antagonist, relieves the itch associated with exogenous opioids, and no 5-HT 3 receptors have been found in the skin (Twycross et al., 2003).
Many other naturally occurring chemicals cause local itch when injected into the skin. These include amines, proteases, growth factors, neuropeptides, opioids, eicosanoids, and cytokines. Some produce itch by causing histamine release from mast cells and/or by sensitizing C-fibers. Some stimulate the nerve endings directly (Twycross et al., 2003).
Neuropathic itch can originate from damage to the nervous system, such as with postherpetic neuralgia, notalgia paresthetica (nerve entrapment of spinal nerve roots), and HIV infection. Paroxysmal itch can occur in multiple sclerosis, whereas unilateral pruritus occurs in brain damage, such as with tumors, infections, or stroke (Twycross et al., 2003).
Neurogenic itch is induced centrally without nerve damage and is associated with increased endogenous or exogenous opioids.
Psychogenic itching is a diagnosis of exclusion when itching occurs in association with neuropsychiatric disease and other causes of itching have been ruled out. No systemic disease is found, and no primary skin lesions are found. Secondary lesions of excoriations and lichenification are found on the parts of the body that can be reached by the fingernails, usually sparing the upper back. Some patients deny they scratch despite witnessed scratching and bleeding excoriations (Fleischer, 2000).
CONDITIONS AND MECHANISMS OF ITCHING
Localized
Atopic eczema (or atopic dermatitis) results from an abnormality of T helper type 2 cells resulting in increased transepidermal water loss. Patients usually have had this condition intermittently all their lives. They often have other atopic conditions such as asthma or hayfever and a family history of atopy (Levine & Levine, 2004).
With bites and infestations, scabies, chiggers, lice, and fleas release histamine into the skin.
Brachioradial pruritus is one of the rare forms of persistent localized itching in normal skin, occurring on the lateral aspect of the arms. It occurs most commonly in fair-skinned persons with significant sun exposure but has also had nerve root damage suggested as a cause (Bueller, Bernhard, & Dubroff, 1999; Winhoven, Coulson & Bottomley, 2004).
Burn pruritus is a frequently reported complication in burn survivors, persisting past the active healing phase. It is believed to be mediated by persistent increased mast cells and histamine release (Hettrick, O’Brien, Laznick et al., 2004).
Contact dermatitis (dermatitis venenata; contact eczema) is caused by irritants, which are substances that can damage cells in anyone if given enough exposure (e.g., soaps), or by a type IV hypersensitivity reaction affecting only sensitized persons. Other variants are contact urticarial, which may be immunological, and photocontact variant, where light transforms substances into irritants or antigens (Levine & Levine, 2004).
Fungal infection with Candida albicans causes candidiasis (moniliasis) of the mouth, vagina, skin, and nails, and in immunocompromised persons, it can cause infections of the esophagus, lungs, and blood (Hall, 2000). Tinea pedis is usually caused by Epidermophyton floccosum, Tricophyton rubrum, or T. mentagrophytes. Tinea cruris has the same causative agents as tinea pedis.
“Virtually anything that itches may create a self-perpetuating itch-scratch cycle” (Fleischer, 2000, p. 90). Lichen simplex chronicus (localized neurodermatitis, lichenified dermatitis) and prurigo nodularis are forms of neurodermatitis. “To understand the importance of lichenification and the symptoms which make patients scratch or rub repeatedly, the reader must understand that it takes over 100,000 scratches to make significant lichenification” (Fleischer, 2000, p. 89).
Nummular eczema (nummular dermatitis; discoid eczema) is associated with xerosis, atopy, and venous stasis.
Pruritus ani is an embarrassing proctologic condition affecting about 5% of the population, characterized by intense itching localized in the anus and perianal skin. Local irritants and psychosomatic factors have been suggested as causes but not proved to be of relevance (Lysy, Sistiery-Ittah, Israelit et al., 2003). Urticaria (hives) are caused by allergic and nonallergic mechanisms, with the final common pathway consisting of histamine and other mediator release from mast cells (Levine & Levine, 2004).
Generalized
“It can be stated almost without exception that any drug systemically administered is capable of causing a skin eruption” (Hall, 2000, p. 82). Enteral or parenteral drugs must always be suspected in a generalized skin eruption.
Essential pruritus is the rarest form of generalized pruritus, and is a diagnosis of exclusion only after drug reactions, uremia, malignancy, liver disease, bullous pemphigoid, AIDS, and intestinal parasites have been ruled out (Hall, 2000).
Liver diseases may precipitate pruritus, especially those with cholestasis. Pruritus occurs in approximately 50% to 70% of patients with primary biliary cirrhosis (Talwalkar et al., 2003).
Itching may occur with any malignancy, and the etiology of paraneoplastic itching is poorly understood. Peripheral T-cell lymphoma and other cutaneous lymphomas are notoriously pruritic. Itch has the highest reported prevalence in Hodgkin’s disease, at 10% to 30% (Fleischer, 2000).
Psoriasis occurs most commonly on the scalp, elbows, and the knees but can occur anywhere. The condition is marked by increased proliferation of epidermal keratinocytes associated with an infiltrate of neutrophils and lymphocytes. Erythematous papulosquamous lesions vary in size and shape and usually have a thick, silvery scale. About 30% of these patients itch (Hall, 2000).
Senile pruritus of the elderly occurs year round, mostly in the scalp, shoulders, sacral areas, and the legs and not necessarily associated with dry skin. It may involve a disorder of keratinization (Hall, 2000).
Uremic pruritus is most often paroxysmal, frequently affecting the forearms and back. It may involve unidentified pruritogenic substances accumulating in dialysis patients as a result of molecular size; other theories implicate xerosis, hyperparathyroidism, hypercalcemia, hyperphosphatemia, elevated plasma histamine levels, and uremic neuropathy (Levine & Levine, 2004). The confusion of etiology can be seen in the statements of other reviewers, who state that for the last 20 years various causes of the pruritus of uremia have been explored, and promising mechanisms have been found to be undependable. Some primary culprits of causation have been touted and eliminated, including excessive parathyroid hormone and calcium phosphate crystals. And “it remains to be established whether the opioidergic system plays a significant role in the pathophysiology of uraemic pruritus” (Mettang, Pauli-Magnus & Alscher, 2002, p. 1561).
Water-induced itching or aquagenic pruritus is pruritus that occurs after contact with water or with sudden temperature changes. It may occur alone or in conjunction with polycythemia vera. Aquagenic pruritus is characterized by itching with a pricking sensation that lasts 15 to 60 minutes. Elevated histamine levels are found in the skin during attacks (Fleischer, 2000; Levine & Levine, 2004).
Winter pruritus (pruritus hiemalis) is most common in the elderly and most prominent on the legs and is due to low humidity in heated air (Hall, 2000).
ASSESSMENT AND MEASUREMENT
Like pain, pruritus is by definition an unmeasurable, subjective sensation. If the itch occurs in conjunction with an observable skin condition, the skin abnormality can be described and measured. But the pruritus itself must be reported by the patient or, if not reported, inferred from a patient’s scratching behavior. Most advanced practice nurses assess a patient’s degree of pruritus by the patient’s report that the itch is minor, moderate, or “driving me crazy.”
In a typical pruritus research study, subjects kept a weekly diary, quantifying the amount of itch they were experiencing and their overall well-being on 5-point scales (Browning, Combes & Mayo, 2003). Another commonly used research tool is the visual analogue scale consisting of a 10-cm line marked 0 (no itch) at one end and 10 (maximum itch) at the other end. This is used to measure pruritus at one point in time (Manenti et al., 2005).
Itch in Normal Skin
Itch occurring without visible abnormalities of the skin is usually generalized. The scratching associated with generalized itch can produce the secondary lesions of excoriations.
For patients already known to have conditions that cause generalized pruritus (e.g., malignancy, renal failure, or cholestatic liver disease), efforts can move directly to treatment for relief.
Whether patients with generalized itch who do not have a probable cause will be subjected to an intense search for occult disease or treated empirically depends on the functional status of the patient and his or her desires.
Itch with Localized Abnormality of the Skin
When pruritus is associated with abnormalities of the skin, the abnormality should be carefully assessed and described. The size of the afflicted area, the types of lesions, and their distribution should all be noted.
A short review of the proper terms and descriptions for primary and secondary lesions of the skin follows (Hall, 2000).
Primary and secondary lesions of the skin often occur together in itchy conditions. Secondary lesions may obscure distinctive primary lesions, but a careful examination usually identifies both the primary and the secondary lesions.
Primary Skin Lesions
▪ Macules range up to 1 cm and are round, flat discolorations of the skin.
▪ Patches are larger than 1 cm, flat discolorations of the skin, like vitiligo and senile freckles.
▪ Papules range up to 1 cm in size and are circumscribed elevated superficial solid lesions. A wheal is a type of papule that is edematous and transitory (present less than 24 hours), like hives and some insect bites.
▪ Plaques are larger than 1 cm and are circumscribed, elevated, superficial, solid lesions.
▪ Nodules range up to 1 cm and are solid lesions with depth; they may be above, level with, or beneath the skin surface.
▪ Vesicles range up to 1 cm and are circumscribed elevations of the skin containing serous fluid.
▪ Bullae are larger than 1 cm and are circumscribed elevations that containing serous fluid (e.g., pemphigoid, second-degree burns).
▪ Pustules vary in size and are circumscribed elevations of the skin that contain purulent fluid.
▪ Petechiae range to 1 cm and are circumscribed deposits of blood or blood pigments in the skin.
▪ Purpura is larger than 1 cm and is a circumscribed deposit of blood or blood pigments in the skin.
▪ Burrows are tunnels in the epidermis caused by insects or larvae, such as in scabies or cutaneous larva migrans.
Secondary Skin Lesions
▪ Scales are shedding dead epidermal cells that may be dry (e.g., psoriasis) or greasy (e.g., dandruff).
▪ Crusts are variously colored masses of skin exudates such as seen in impetigo or infected dermatitis.
▪ Excoriations are abrasions of the skin, usually superficial and traumatic.
▪ Fissures are linear breaks in the skin, sharply defined with abrupt walls.
▪ Ulcers are irregularly sized and shaped excavations of the skin extending into the dermis or deeper.
▪ Scars are formations of connective tissue replacing tissue lost through injury or disease.
▪ Keloids are hypertrophic scars beyond the borders of the original injury.
▪ Lichenification is a diffuse area of thickening and scaling with resultant increase in the skin lines and markings (Hall, 2000, pp. 14-17).
HISTORY AND PHYSICAL EXAMINATION
History
In the ideal medical interview, the patient describes his or her symptoms freely and spontaneously and stops when what needs to be communicated has been expressed. The clinician then repeats any information that needs clarification and asks any indicated further questions. When the current problems have been discussed, the clinician then asks questions to uncover any additional problems.
A person suffering from itch may fail to communicate that fact. A patient with intermittent itch may forget to mention it, and even a patient with constant itch may put it out of mind to discuss more urgent matters. If a patient is observed scratching, questions about itch obviously need to be asked. For others, the symptom of itch may be uncovered with general dermatologic questions: Any skin problems? Any lumps, bumps, rashes, itching?
When any symptom, such as itch, is positive, it needs to be further characterized. Has this been a lifelong problem, a recurrent one, or a new one? If new, when did it start? Is the itching localized or general, constant or intermittent? When does it occur (if intermittent), or when is it worst (if constant)? (For a patient who is bothered by itch only at night, morning treatment is unnecessary.) What makes it better; what makes it worse? What treatments have been tried, and with what effect?
The ideal medical interview will always include a careful and complete drug history that includes all prescription, over-the-counter, and recreational drugs. This is especially important for persons troubled by pruritus.
Physical Examination
The physical examination must include the entire skin surface, with particular attention to those areas the patient has indicated as itchy. All abnormalities of the skin and mucous membranes should be described and recorded using standard dermatologic terminology, with careful measurements of areas involved.
The negative finding of no rash or lesions is equally important.
DIAGNOSTICS
Localized Pruritus
When the findings of the history and physical examination have identified a likely diagnosis with an easily used treatment, a presumptive diagnosis and therapeutic trial are warranted. For instance, if the inflamed itchy areas coincide with areas of tape applied to the skin, an acquired tape sensitivity is likely. When the measures of avoidance of tape, oral antihistamines, locally applied antihistamine cream, or possibly mild steroid cream resolve the problem, the diagnosis is confirmed.
Infestations and fungal infections may also be treated presumptively or may be confirmed with microscopic examination.
Occasionally, a localized outbreak defies identification and treatment and must be referred to a dermatologist. A skin biopsy with special stains may be required for a definitive diagnosis (Hall, 2000).
Generalized Pruritus
As stated, a patient with known renal failure, malignancy, or bile duct obstruction probably needs no further investigation into the cause of generalized pruritus. An elderly patient may certainly be treated for a presumptive diagnosis of senile pruritus or winter pruritus (Hall, 2000). For others, simple laboratory tests can identify or rule out kidney, liver, or endocrine disorders. The search for an occult malignancy is much more difficult, and whether it is undertaken should be decided by the patient.
In a sense, all routine medical care is a search for occult disease, especially malignancy, but when a person presents with generalized persistent pruritus and wants an answer, the search has more intensity. It starts with the complete history and physical examination, including a rectal examination and, for women, a pelvic examination. A chest radiograph or computed tomography scan is warranted, especially for smokers. Stool studies for parasites and occult blood should be done. Older patients who have not had a recent colonoscopy should have one performed (Hall, 2000). If no other cause is found, a skin biopsy of normal skin may find occult pemphigoid (Greaves & Wall, 1999). If that is also normal, one of the diagnoses of exclusion—psychogenic pruritus or essential pruritus—may be made, with treatment as described later.
INTERVENTION AND TREATMENT
General Measures
“Improved understanding of the pathophysiology of itch has led to modest advances in treatment. No doubt in time this progress will lead to selective topical antipruritics. Topical corticosteroids are not direct antipruritics and should not be used as such, although they effectively relieve itching secondary to inflammatory skin disease” (Yosipovitch, Greaves, & Schmelz, 2003, p. 693).
All of the following suggested measures may or may not be effective and to varying degrees. Individual responses to treatment must be carefully followed. When success occurs, that treatment should be continued, even if a reason for the success is not known.
Itch is usually intensified by heat, so cooling measures may be helpful for any patient with pruritus. Cool clothes, a cool but not dry ambient temperature, and tepid showers or baths may help (Twycross et al., 2003).
Because histamine is the known pruritogen responsible for all or some of the itching in most pruritic conditions, antihistamines remain a mainstay of pruritus treatment. Antihistamine medication is available in both oral and topical forms. The sedation of first-generation antihistamines may be part of the relief provided and is especially helpful and acceptable for nocturnal pruritus.
Antihistamines come from various chemical classes (Table 34-1) (Werth, 2004, p. 2457), and sometimes an antihistamine from one class may have more effect and fewer side effects than one from a different chemical class for a particular patient. Many patients will already know which antihistamines work well for them. If a patient does not know and a search needs to be made for a more effective, better tolerated antihistamine, it makes sense to try one from an untried chemical class.
| Antihistamine Group | Generic Name |
|---|---|
| First-Generation H 1-Type Antihistamines | |
| Alkylamine | Brompheniramine (Dimetapp) |
| Chorpheniramine (Chlor-Trimeton) | |
| Aminoalkyl ether (ethanolamine) | Clemastine fumarate |
| Diphenhydramine (Benadryl) | |
| Ethylenediamine | Pyrilamine (Triaminic) |
| Phenothiazine | Promethazine (Phenergan) |
| Trimeprazine (Temaril) | |
| Piperidine | Azatadine |
| Cyproheptadine | |
| Diphenylpyraline | |
| Piperazine | Chlorcyclizine |
| Hydroxyzine (Atarax) | |
| Second-Generation H 1-Type Antihistamines | |
| Alkylamine | Acrivastine (combined with pseudoephedrine in allergy medication) |
| Piperidine | Astemizole (Hismanal) |
| Loratidine (Claritin) | |
| Fexofenadine (Allegra) | |
| Piperazine | Cetirizine (Zyrtec) |
| H 2-Type Antihistamines | Cimetidine (Tagamet) |
| Ranitidine (Zantac) | |
| Famotidine | |
| Nizatidine | |
| H 1– and H 2-Type Antihistamines | Doxepin (Sinequan) |
Specific Measures
Aquagenic Pruritus
Treatments include photochemotherapy, ultraviolet B (UVB) phototherapy, first-generation antihistamines, alkalinization of bath water, and intramuscular triamcinalone (Levine & Levine, 2004). If associated with polycythemia vera, the first treatment is aspirin 300 mg as needed, which is usually effective for 12 to 24 hours. If a patient is receiving interferon α (Intron-A) as treatment for polycythemia vera, the itch is usually improved. Paroxetine (Paxil) has also been shown to be effective (Twycross et al., 2003).
Atopic Dermatitis
Doxepin (Sinequan) is a tricyclic compound with high potency as an antihistamine. It is available in a cream (Zonalon) and is effective in suppressing the pruritus of atopic eczema. However, it is absorbed through the skin and, like other antihistamines, can be sedating (Yosipovitch et al., 2003).
Standard treatments include intermediate potency topical corticosteroids, such as Cutivate, Valisone, Diprosone, or oral prednisone (Orapred, Deltasone) for temporary therapy of severe flares; azathioprine (Imuran); cyclosporine (Neoral); first-generation antihistamines for nighttime sedation; UVB phototherapy; photochemotherapy (PUVA); evening primrose oil; Chinese herbs; and emollients applied at least twice daily, particularly during the winter months (Smith, 2000; Tofte & Hanifin, 2001).
Capsaicin cream 0.025% to 0.075% is effective but can cause irritation at first. The irritation can be reduced by using the topical anesthetic eutectic mixture of local anesthetics (EMLA) cream (Yosipovitch et al., 2003).
Brachioradial Pruritus
This rare condition responds poorly to the usual treatments of topical or oral corticosteroids and antihistamines or to spinal manipulation and capsaicin. Early reports have found good response with gabapentin (Neurontin) (Bueller et al., 1999; Winhoven et al., 2004).
Burn Pruritus
The standard treatment is to use oral antihistamines and topical lotions such as Revive (Dermalife, Albuquerque, N.M.) lotion or Corrective Concepts (Corrective Concepts Co., Dallas, Tex.) in the attempt to prevent the rubbing or scratching that can damage healed and grafted skin. Research into additional measures when the standard treatment is insufficient has shown benefit from massage (Field et al., 2000), transcutaneous electrical nerve stimulation treatment (Hettrick et al., 2004), and scheduled rather than as-needed dosage of H 1 and H 2 blockers (Baker, Zeller, Klein et al., 2001).
Cholestatic Pruritus
Practice guidelines from the American Association for the Study of Liver Disease list treatments for cholestatic pruritus as, first, bile acid–binding resins like cholestyramine, a treatment that is at least partly effective but unpalatable and that can interfere with other medications, and, second, rifampicin (rifampin), which may help pruritus but can cause further liver damage (Heathcote, 2000). All other treatments, including naltrexone (Depade), phenobarbitol and propofol (Diprivan), antihistamines, S-adenosylmethionine (SAMe, a dietary supplement), phototherapy, anticonvulsants, ondansetron (Zofran), and plasmaphersis, are considered experimental (Heathcote, 2000).
A later study showed significant relief of cholestatic pruritus in 9 of 20 patients treated with naltrexone. (Note that naltrexone cannot be used for patients who require opioids for pain control.) In patients without pain and with severe pruritus, this opioid antagonist may help. One study determined that side effects occurred in the first 48 hours and were consistent with opioid withdrawal. They resolved spontaneously within 2 days of treatment, and the authors concluded, “Naltrexone can be considered as an alternate option to treat pruritus of cholestasis” (Terg et al., 2002).
A serendipitous report of patients treated with sertraline (Zoloft) for depression who had improvement of their cholestatic pruritus led to a study that showed improvement in the cholestatic pruritus of nondepressed patients as well (Browning et al., 2003).
Drug Eruptions
The most important first step is to attempt to identify the causative drug and stop it. If several drugs seem equally likely, all of them should be discontinued. If the patient’s reaction is mild and subsides when the drugs are stopped, no other treatment may be necessary. If the reaction is severe, systemic corticosteroids may be required to quiet it. Antihistamines (unless an antihistamine is the inciting medication) can be given for relief of pruritus in either case (Hall, 2000).
If some of the discontinued drugs are considered essential, they can cautiously be resumed, one at a time, after the reaction is controlled.
Dry Skin
Even for patients with other probable causes of itching, the use of an emollient cream may eliminate the portion of itch caused by dry skin. Bathing should be limited, and soap substitutes such as bath gels should be used. Sedating first-generation antihistamines help with nighttime sleep (Levine & Levine, 2004).
Essential Pruritus
This diagnosis (of exclusion) of generalized pruritus in normal-appearing skin is treated in the same manner as senile and winter pruritus (Hall, 2000).
Malignancies
“Paraneoplastic itch associated with solid tumors is not eased by corticosteroids or cimetidine. However, paroxetine (Paxil) is almost always beneficial, often within 24 hours” (Twycross et al., 2003).
For Hodgkin’s disease, the usual treatments of radiotherapy and/or chemotherapy will relieve itch if otherwise effective. Corticosteroids usually relieve itch in late-stage disease (Twycross et al., 2003).
Neurodermatitis
Locally circumscribed neurodermatitis (lichen simplex chronicus) is an itchy dermatitis with a prolonged course and is most common in Asians. The usual treatment is steroid creams. For persons in whom that was not sufficiently helpful, the application of an aspirin-dichloromethane solution reduced pruritus and improved healing (Yosipovitch, Sugeng, Chan et al., 2001).
Thalidomide reduced the signs and symptoms of prurigo nodularis in HIV-infected patients, although one-third of the study subjects developed a degree of thalidomide peripheral neuropathy (Maurer, Poncelet, & Berger, 2004).
Pruritus Ani
Pruritus ani with dermatosis may be treated for up to 1 month with mild steroid cream (Lysy et al., 2003). “When pruritus ani has no demonstrable aetiology, it is often described as idiopathic, and advice regarding hygiene and drying methods is usually given, with poor results” (p. 1323). Some patients, however, do respond to conservative measures: gentle cleansing with an emulsifying ointment and drying (preferably with a hair dryer) and avoidance of underwear that traps sweat such as nylon and acrylic (Lysy et al., 2003). In their study, Lysy and colleagues treated patients with dilute capsaicin cream (0.006% or 0.012%). It was far more effective than placebo menthol cream for 31 of the 44 patients in the study, and long-term follow-up showed it continued to be, with few side effects (Lysy et al., 2003).
Senile Pruritus
The treatment of senile pruritus is the same as that for winter pruritus (see p. 514). In addition to the treatment recommendations for winter pruritus, two or three injections of triamcinalone acetonide suspension 30 mg (Kenalog-40) intramuscularly every 4 to 6 weeks can be beneficial (Hall, 2000).
Uremic Pruritus
Because the itch associated with chronic uremia has been recognized for over 100 years, it must be assumed to be due to uremia and not just dialysis. In fact, the incidence of uremic pruritus has fallen. In the early 1970s, when dialysis was new, the incidence of pruritus was reported as 85%. By the late 1980s it fell to 50% to 60%, and now the prevalence of renal itch among patients on dialysis is estimated at between 22% and 48% (Manenti et al., 2005).
The physiology of uremic pruritus is complex and not well understood, and many treatments have been tried, with varying success. “Most of the success stories have turned into reports of failure” (Mettang et al., 2002). One such story involved ondansetron (Zofran), where early reports of success were followed by a controlled trial that showed no difference between it and placebo (Murphy, Reaich, Pai et al., 2003). “Whenever a new treatment option is reported to be effective, some time elapses before conflicting results are published; in the meantime, the mood of patients and physicians changes from euphoria to disillusionment. This happened with erythropoietin and naltrexone” (Mettang et al., 2002). Other researchers still believe that naltrexone is helpful in a subset of patients and “might be considered as a second-line treatment” (Legroux-Crespel, Cledes, & Misery, 2004).
Other researchers state, “Pruritus is the most distressing symptom in haemodialysis (HD) patients. Its aetiology has not yet been delineated, and thus there are no good therapeutical options” (Weisshaar, Dunker, Rohl et al., 2004). Their study concluded that 5-HT 3 receptor blockers such as tropisetron and ondansetron (Zofran) and the antihistamine cetirizine (Zyrtec) do not reduce itching in hemodialysis patients.
Two studies of gabapentin treatment have had positive conclusions.
“[O]ur data suggest that gabapentin could be considered an effective and safe alternative treatment for uremic pruritus” (Manenti et al., 2005). “Our study shows that gabapentin is safe and effective for treating uraemic pruritus in haemodialysis patients” (Gunal, Ozalp, Yoldas et al., 2004).
The nondrug treatment of UVB therapy has been used with some success (Gilchrest, Rowe, Brown et al., 1997). Levine and Levine (2004) mark it as a clear treatment of choice. Their other listed possible treatments are cholestyramine 4 g orally twice daily, activated charcoal 6 g orally daily divided into four to six doses, first-generation antihistamines, emollients, acupuncture, or naltrexone 50 mg orally daily (Levine & Levine, 2004). Naltrexone should never be given to patients requiring opioids for pain control.
Capsaicin use in uremic pruritus received a weak endorsement as a possible co-medication (Weisshaar, Dunker & Gallnick, 2003).
Thalidomide is also recommended, although it is teratogenic and must not be used in women who may become pregnant (Twycross et al., 2003).
Urticaria
Chronic idiopathic urticaria is the most common type of chronic urticaria, and pruritus is its most prominent symptom. Antihistamines are effective, but the side effects of first-generation antihistamines for persons who need constant suppressive treatment can limit their use. Some promising second-generation nonsedating antihistamines (terfenadine and astemizole) were taken off the market in 1998 and 1999 because of the rare occurrence of a potentially fatal cardiac arrhythmia, torsades de pointes. Other second-generation antihistamines on the market do not have this danger and have been shown to be effective for urticaria, with few side effects (Brown & Roberts, 2001; Ring, Hein, Gauger et al., 2001).
Winter Pruritus
“Treatment of winter pruritus consists of the following:
1. Bathing should involve as cool water … and as little soap as possible.
2. A bland soap such as Dove, Oilatum, Cetaphil, or Basis is used sparingly.
3. An oil is added to the bath water, such as Lubath, RoBathol, Nivea, or Alpha-Keri. (The patient should be warned to avoid slipping in the tub.)
5. A low-potency corticosteroid ointment applied twice-daily is effective.
6. Oral antihistamines are sometimes effective, such as chlorpheniramine (Chlor-Trimeton), 4 mg hs or qid, or diphenhydramine (Benedryl), 50 mg hs” (Hall, 2000, p. 98).
EDUCATION, EVALUATION, AND PLAN FOR FOLLOW-UP
The conversation about a patient’s problem with itching begins with the first mention of it by the patient, a family member or friend, or the clinician and continues until either the problem is completely resolved or the patient dies. A part of this communication is the mutual education of the patient by the clinician and of the clinician by the patient.
The clinician will attempt to communicate everything he or she knows about the cause, treatment, and amelioration of itch, including the preventative measures that are especially important in contact allergies, winter pruritus, and dry skin pruritus.
When the patient has a specific diagnosis, particularly if it is a relatively rare one, the clinician may want to share his or her research with the patient and family. Of course, today many patients and families are doing their own research on the Internet. Some information from the Internet is credible; some is not.
Communication with the patient involves careful listening to determine the patient and family’s understanding of the cause and treatment of the patient’s pruritus. As long as the symptoms persist, the communication will include a continuing careful review of what the patient and family have used or done, or not used or done, and why.
The patient may have difficulties with treatments prescribed by the clinician and be reluctant to admit this. Problems with the cost, side effects, or inconvenience of a treatment may prevent a patient from following the clinician’s advice. The clinician needs to elicit this information and take it into account while making further plans with the patient.
On the other hand, a clinician may have little choice but to continue to follow a patient who is relying on dubious authorities and using expensive useless (or harmful) treatments. Over time, these treatments will work or not work. If they do, that is great. If not, the patient and family may once again be willing to try other recommendations.
Mrs. D. is a 78-year-old widowed European American woman referred for hospice care by her case manager at an acute care hospital. The hospice receives the referral on April 12, with the information that her terminal diagnosis is end-stage liver disease. The patient’s family wavers about accepting and agreeing to end-of-life care, and her admission to inpatient hospice care is delayed until April 25.
Her other medical problems are heart failure, a systolic ejection murmur, osteoporosis, Parkinson’s disease, and asthmatic chronic obstructive pulmonary disease.
Her surgical history includes cholecystectomy, appendectomy, removal of a left ankle tumor, and bilateral venous stripping.
She is allergic to aspirin, iodine, sulfa, and codeine.
On her April 7 admission to the acute care hospital, her home medications were continued, the following being ordered: Os-Cal, ferrous sulfate, Klor-Con, carbidopa, levodopa, Primidone, Keflex, Advair, Xopenex, omeprazole, Evista, folic acid, Lasix, and Zaroxolyn. Medication records from the hospital add Inderal, Bentyl, Chronulac, Insulin, Flovent, Serevent, Tylenol, Demerol started April 9, Benadryl started April 9 for nausea, Mephyton from April 11 to 13, Risperdal started April 13, morphine started April 14, and Reglan and Duragesic 25 mcg patch started on April 24.
When she arrives at the hospice, the staff is surprised that her most pressing problems are rash and pruritus, which were not mentioned in her written records or verbal report.
Mrs. D.’s only complaint is itching all over. She has a bright red, confluent macular-papular rash of her arms, neck, chest, and thighs. She has 0.5- to 1-cm blisters of her inner left knee, perhaps where her latex catheter tube has been lying. She also has a fungal-appearing rash of her groin and axillae.
Although she has compromised liver and renal function, it is unlikely her pruritus is associated with either condition. Cholestatic and uremic itching occur in normal-appearing skin, and she has a rash. Because this is pruritus in abnormal skin, the differential diagnosis includes drug reaction, contact dermatitis, and candidiasis.
A drug reaction seems likely from the appearance, extent, and severity of the rash and the fact that a woman known to be allergic to four medications has received approximately 28 different medications in the previous 17 days, some of them new to her. Contact dermatitis also seems possible. The adhesive of Duragesic patches can cause contact dermatitis, and she may have developed a latex sensitivity. With the wide distribution of her skin reaction, she might also have an allergy to something like the hospital sheets or the soap with which they are washed.
None of her previously given medications are continued. The fentanyl patch is removed, and her indwelling catheter is changed to a silicone one. Paper sheets are not yet changed; the clinician will wait to see if other measures are sufficient. To treat the probable drug reaction, we start oral dexamethasone (Decadron) 4 mg orally three times daily and hydroxazine (Atarax) 50 mg orally three times daily. In hospice, essential oils are also used for symptom control, so a spritzer of dilute lavender oil to spray on the itchy places as needed is given to the patient.
Her rash and pruritus fade with the first doses of medication and come under good control within 36 hours. The medications are continued without change to consolidate the improvement.
On April 28, she is noted to have a vaginal discharge. She is given fluconazole (Diflucan) one 150-mg pill only, for vaginal candidiasis. The vaginal discharge and groin and axillary rash resolve completely over the next few days.
On May 9, her skin is normal but dry, and she is able to tolerate and enjoy the application of lavender oil to the skin.
On May 10, the Atarax order is changed from “routine three times daily” to “three times daily only as needed for itch,” and she takes no more of it.
On May 17, the Decadron is reduced to 4 mg twice daily, with no ill effects.
By May 19, she is having trouble swallowing, oral medications are discontinued, and the Decadron is changed to 4 mg per rectum every 24 hours.
On May 20, she has an upper gastrointestinal hemorrhage and dies.
The exact cause of this patient’s severe rash and pruritus will never be known. However, rapid empiric measures (removal of possible offending substances, systemic steroids, and a first-generation antihistamine) relieved the problems and gave her 3 weeks of comfortable good time with her family before her death.
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